NEWER TESTS FOR GLAUCOMA

By Dr.Shruthy Vaishali

Moderator – Prof. Dr.K.N.Jha

Dr.A.R.Rajalakshmi

• Glaucoma is one of the leading causes of blindness worldwide. Early diagnosis of glaucoma is critical to prevent permanent structural damage and irreversible vision loss.

• Chronic, progressive optic neuropathy characterised by optic disc and retinal nerve fibre layer changes with corresponding visual field defects and with raised IOP

The assessment of glaucoma is done with these following parameters:

• IOP Measurement

• Status of anterior chamber angle

• Optic nerve head changes

• Abnormalities in visual field.

IOP Measurement

• Goldmann Applanation tonometry – Gold standard.

Other newer types are:

• Dynamic contour tonometry

• Ocular Response Analyser

• Rebound Tonometry

Dynamic Contour Tonometry

• Principle: when the contours of the cornea and tonometermatch, then the pressure measured at the surface of the eye equals the pressure inside the eye

• It is not affected by central corneal thickness.

• It has a disposable tip which prevents contamination.

• Numerical display of result .

• No need for calibration.

• It is superior to Goldmann applanationtonometry.

Ocular Response Analyser

It directs the air jet against the cornea and measures not one but two pressures at which applanation occurs

1) when the air jet flattens the cornea as the cornea is bent inward and 2) as the air jet lessens in force and the cornea recovers.

• The first is the resting intraocular pressure.

• The difference between the first and the second applanation pressure is called corneal hysteresis

• Corneal hysteresis is a measure of the viscous dampening and, hence, the biomechanical properties of the cornea

Rebound Tonometry

• A 1.8mm diameter plastic ball on a stainless steel wire is held in place by an electromagnetic field in a handheld battery-powered device.

• When the ball hits the cornea, the ball and wire decelerate; the deceleration is more rapid if the IOP is high and slower if the IOP is low. The speed of deceleration is measured and is converted by the device into IOP.

• Influenced by central corneal thickness

• Affected by other biomechanical properties of the cornea, including corneal hysteresis and corneal resistance factor.

Anterior Chamber Angle Assessment

• Gonioscopy

• Imaging Techniques– Anterior Segment Optical Coherence Tomography

(ASOCT)

– Ultrasound biomicroscopy(UBM)

– Scanning Peripheral Anterior Chamber Depth Analyzer (SPAC)

– EyeCam

Ultrasound Biomicroscopy

• In the principle of ultrasonography, the depth of tissue structures is determined by directly measuring the time delay of returning ultrasound signal

• Requires contact with the eye, and a coupling medium is necessary such that scanning must be performed through an immersion bath.

• Operates at 50 MHz

• Tissue penetration is approximately 4 to 5 mm

• Standard measurements include: 1) Angle opening distance (AOD). 2) Angle recess area (ARA)

• Advantages: Can assess angle through opaque media.

• Limitations: longer image acquisition times, and the need for a skilled operator

Anterior Segment Optical Coherence Tomography

• Optical Coherence Tomography, or OCT, is a noncontact, noninvasive imaging technique used to obtain high resolution cross-sectional images of the retina and anterior segment.

Priciples:

• Interferometry

• Low coherence light in near infra-red range

A low coherence infrared light (820nm) is projected on the beam splitter

One beam is directed through the ocular media (Probe beam) and the other beam is focused on to a reference mirror at known variable position (Reference beam)

Probe beam is reflected back from the boundaries between the retinal microstructures and is scattered differently from tissues with different optical properties

The distance between the beam-splitter and the reference mirror varies continuously and when equal, the light reflected from the retinal tissue and the reference mirror interacts to produce an interface pattern (interference)

Detected by a camera detector and processed into a signal

Applications in Glaucoma

• Angle Imaging• Screening for angle closure• Studying the effect of Peripheral Iridotomy• Imaging of blebs• Analysis of tube position in implant surgeries • Pachymetry

• Non-contact

– No possibility of indentation, so no corneal abrasion or punctate epithelial erosion as seen in UBM

• Shorter imaging time

• Rapid image acquisition

Scanning Peripheral AC Depth Analyser (SPAC)

• Takes consecutive slit lamp images from optical axis of the eye to the limbus

• Images are captured on a charge-coupled device camera by the computer

• Total of 21 images are taken of AC depth at 0.4 mm intervals & converted into numerical and categorical grades by comparison with normative database

EyeCam

• The EyeCam is a new technology originally designed to yield wide-field photographs of the pediatric fundus for the diagnosis and management of posterior segment diseases.With modifications in the optical technique and the inclusion of a 130 degree lens, the device can be used to visualize angle structures in a manner similar to direct gonioscopy.

Limitations

• Unable to provide quantitative measurements

• takes longer than gonioscopy (about 5–10 min per eye).

• more expensive and additional space is required for supine examination.

• It is not known if supine positioning would widen the angle due to the effect of gravity on the lens–iris diaphragm

Imaging Techniques for optic Disc and RNFL evaluation in glaucoma

• Confocal scanning laser ophthalmoscopy(HRT ; Heidelberg Retinal Tomography )

• Scanning Laser polarimetry (GDx )

• Optical Coherence Tomography

Confocal scanning laser ophthalmoscopy

• Confocal = conjugate + focal

• i.e. the focal plane of the retina and the focal plane of the image sensor are located at conjugate positions

• Confocality achieved by placing pinholes in front of the detector which is conjugate to the laser focus

• Spatial filters (pin holes) are used to eliminate out-of-focus light or flare

• Size of the pin hole – determines degree of confocality

• Smaller pin hole – highly confocal image

• 670-nm diode laser beam focused in the x-axis and y-axis (horizontal and vertical dimensions) of the ONH, perpendicular to the z-axis (axis along the optic nerve)

• Reflected image from this plane is captured as a 2-dimensional scan

• Successive equidistant images are obtained (64 in total)• 3-dimensional construct of the ONH region• Topographic map• Calculation of cup-to-disc (C/D) ratio• Rim area• Other optic disc parameters

CUP■ C/D Ratio■ Shape■ AsymmetryRIM■ Area & Volume■ AsymmetryRNFL■ Height Variation Contour■ Thickness■ Asymmetry

Topography Image

• False color image

• Similar to gray scale of VF printout

• Provides size, shape and location of cup

Scanning Laser Polarimetry

• Scanning laser polarimetry (SLP) is designed to quantitatively assess the thickness of the peripapillary RNFL.

• It is based on the measurement of a physical property called retardation of an illuminating laser beam passing through the birefringentRNFL.

• Birefringence in the nerve fiber layer arises from the parallel arrangement of microtubules within the axons of this layer.

• Form birefringence• Splitting of a light wave by a polar material into two

components• Two components travel at different velocities and creates a

relative phase shift (retardation)• The amount of retardation is proportional to thickness of

polar tissue (RNFL)• The RNFL behaves as a polar tissue because of the

microtubules (with diameter smaller than the wavelength of light)

• The greater the number of microtubules, the greater the retardation.The greater the retardation the greater is the tissue thickness

• A 780-nm diode confocal scanning laser with an integrated polarimeter is focused on the retina.

• The backscattered light that doubly passes through the RNFL shows retardation that is measured by a polarization detection unit.

• The total data acquisition takes 0.7 seconds.

• A reflectance image of the scanned image is produced.

Nerve Fiber Layer Map• The Nerve Fiber Layer Map is

a color map depicting the different RNFL levels in the 20° x 20° area surrounding the optic nerve head (ONH).

• RNFL is represented using a color scale, with dark blue representing smaller RNFL values (smaller phase shift) and generally bright red representing larger RNFL values (greater phase shift).

• Symmetry Analysis report, the TSNIT (Temporal-Superior-Nasal-Inferior-Temporal) nerve fiber layer graph displays the normal range (shaded area) and patient’s values of RNFL developed from the measurement data obtained along the Calculation Circle.

• TSNIT Average :This parameter evaluates the average RNFL (μm) in the Calculation Circle. ( Normal 46 -68 μm)

• Superior Average: This is the average of all pixels (μm) in the superior 120 degrees of the Calculation Circle. ( Normal 55 - 85 μm)

• Inferior Average : This is the average of all pixels (μm) in the inferior 120 degrees of the Calculation Circle. ( Normal 40 - 75 μm)

• The Nerve Fiber Indicator (NFI) for GDx is an algorithm that analyzes the entire RNFL profile.

Advantages

• Easy to operate

• Does not require pupillary dilation

• Comparison with age matched normative database

• Good reproducibility

• Does not require a reference plane.

Limitations

• Does not measure actual RNFL thickness

• Limited use in moderate/advanced glaucoma.

• Difficult in very small pupil and media opacities.

• Requires wider database for Indian population.

• Young patients database not available.

OCT Glaucoma Scans

• The Fast Optic Disc scan

• The Fast RNFL Thickness scan

Fast Optic Disc Scan

The patient fixes on the target, which is automatically placed at the edge of the scan window so that the optic nerve is viewed toward the center of the video window. The operator then moves the scan so that the star pattern is centered on the optic nerve head. Centering can be aided by clicking on the scan window to view the white centering lines.

• "optic nerve head analysis" protocol

The Fast RNFL Thickness scan

• Nerve fiber layer thickness can be evaluated with the "Fast RNFL Thickness" scan. This is a circular scan that requires the operator to place the circle so that the center of the circle is centered on the optic nerve head.

• The analysis software places lines on the top and bottom of the nerve fiber layer and the distance between the two lines is interpreted to be the thickness of the nerve fiber layer

• Ganglion cell analysis

• The ganglion cell layer is thickest in the perimacular region and decreased total macular thickness has been observed in glaucomatous eyes likely due to thinning of the ganglion cell layer in this region.

Perimetry

• Standard automated perimetry detects a visual field defect when about 40% of retinal ganglion cells are lost.

• So it is preferable to detect damage at earlier stages given the irreversible nature of vision loss in glaucoma.

Recent advances in perimetry

• SWAP-Short wave-length automated perimetry

• FDT-Frequency Doubling Technology perimetry

• HPRP-High Pass resolution perimetry

• High Spatial Resolution perimetry

• Motion Detection Perimetry

• Heidelberg Edge perimetry

• RareBit perimetry

Short Wavelenght Automated Perimetry

• Also know as Blue-on-Yellow perimetry

• Here yellow backgroud light(530nm) at a luminance of 100cd/m2 suppresses the red and green cones.

• The blue cones are stimulated by a GoldmannSize V(1.7˚) light with a narrow band short wavelenght interference filter (440nm) with a duration of 200 millisecond.

Advantages:

• Very high sensitivity and specificity.

• Detects glaucomatous changes earlier than standard automated perimetry

Disadvantages

• Increased patient fatigue

• Long adaptation time

• Bright yellow background is very intense and the blue stimuli are hard to perceive

Frequency Doubling Technology perimetry

• Frequency doubling technology (FDT) essentially creates an image that appears double its actual spatial frequency, in which approximately twice as many light and dark bars are usually present .

• This perimetry test does not depend on the appearance of the target but rather the minimum contrast needed to detect the stimulus at different locations in the visual field.

• The first generation Frequency Doubling Technology

• In the first generation FDT perimeter, each target is displayed as a 10-degree-diameter square, the central stimulus which is presented as a 5-degree-diameter circle.

The second generation Humphrey Matrix

• The ability to monitor eye fixation.

• Threshold testing on the Humphrey Matrix uses smaller targets that are presented along a grid. In addition, greater spatial resolution is available with 24-2, 30-2, 10-2, and macular threshold tests.

• 54 targets

• High sensitivity and specificity.

• Detecting early visual field loss compared to SAP

• It is comparatively faster

• FDT has been reported to have both lower intra-and inter-test variability compared to SAP, which suggests it may be a useful test to monitor long-term progression of visual field loss.

• Relatively inexpensive, efficient, and non-operator dependent nature of the test.

• The FDT machines are relatively portable and thus may lend itself to use in community screenings for glaucoma.

Heidelberg Edge Perimetry

• It uses a unique stimulus called Flicker Defined Form.

• A round stimulus is created by reversing the phase of flickering black and white dots, thereby forming illusory outlines. The test uses randomly flickering points in medium illumination (50 cd/m²).

• The background remains the same during the whole test. Background luminance is 50 cd/m2, the marker showing time is 400 ms, and the frequency is 15 Hz.

High Pass Resolution Perimetry

• In this method along with detection, the resolving thresholds are also measured.

• The test target consists of bright circular cores surrounded by dark borders.

• It tests 50 targets in 30˚central visual field.• Main advantages are shorter test time and the

strong preference by patients .• The sensitivity and specificity better than

conventional perimetry. A minor disadvantage was its slightly less precise spatial definition of field defects.

Rarebit Perimetry

• RareBit Perimetry depends on minute stimuli ("rare" bits or "microdots") .

• 24 rectangular test areas .

High Spatial Resolution Automated Perimetry

• High spatial resolution perimetry was performed using a Humphrey automated perimeter by measuring luminance sensitivity across a 9 by 9 degree custom grid of 100 test locations with a separation between adjacent locations of 1 degree

• in glaucomatous eyes fine luminance sensitivity loss was present .

• Limitation : high intratest variability.

Motion Detection Perimetry

• It measures the patients ability to detect a coherent shift in position of dots in a circular area against a background of non-moving dots.

• Its sensitivity is superior to conventional automated perimetry.

OCT angiography

• Using OCT angiography, reduced peripapillaryretinal perfusion in glaucomatous eyes can be visualized as focal defects and quantified as peripapillary flow index and peripapillaryvessel density, with high repeatability and reproducibility. Quantitative OCT angiography may have value in future studies to determine its potential usefulness in glaucoma evaluation.

Detection of Apoptosing Retinal Cells

• The DARC Technology (Detection of Apoptosing Retinal Cells) is an innovative technique that uses the unique optical properties of the eye to allow direct visualization of nerve cells dying through apoptosis, identified by fluorescent-labeledannexin V.

• Thank you